What is the cause?
Recently, there have been several medication shortages of medicines that many people need to take every day in order to survive. The sad thing is that medication shortages are not new, but are increasing in frequency. Why is this happening? What impact does it have on the health of the individuals who can’t take their medications? How do we correct this issue?
Medication shortages are increasing are across the United States. At any given time, there are shortages of well over 100 drugs. This isn’t a new problem. Since 2007, there has been shortages of more than 100 different medications per year. According to the Drug Information Service at the University of Utah Health Care, which tracks the number of shortages per year, the highest number ever (267) was reached in 2011. The shortages are involving an increasing number of drugs without a feasible alternative and lasting longer than in the past, in some cases more than eight years. Many of these medications are used for anesthesia, palliative care, septic shock, controlled substances, local anesthetics, antibiotics, electrolytes, vaccines, medical supplies, like sterile water, and emergency injectables, like “crash cart” drugs. This has resulted in hospitals having to ration lifesaving treatments. A 2018 survey of hospital-based pharmacists reported that 55% had a shortage of 21 or more drugs within the last six months, 27% had weekly shortages and 66% had daily shortages. The same survey also discovered that 71% of the hospitals were unable to provide patients with a recommended drug or treatment due to shortages, which led to delays in treatment and less effective drugs being substituted for the preferred medication that was unavailable.
In response to all of these shortages, the Food and Drug Administration (FDA) created the Agency Drug Shortages Task Force in July 2018. This committee is responsible for investigating the root causes of shortages and proposing long-term resolutions to Congress. While the Task Force is led by FDA, it includes officials from the Department of Defense, Centers for Medicare and Medicaid Services (CMS), Federal Trade Commission, Department of Health and Human Services (HHS), Veteran Affairs and Office of the Assistant Secretary for Preparedness and Response. To get a better understanding of the shortage issue, the task force commissioned a team of FDA economists and scientists to analyze the data of the 163 drugs that experienced shortages between 2013 and 2017. The researchers found that 63% of the drugs’ shortages stemmed from supply disruptions tied to product quality or manufacturing issues, 18% stemmed from unknown reasons, 12% stemmed from unanticipated increases in demand, 5% occurred after natural disasters and 3% stemmed from product discontinuations. An analysis in the report found that 60% of the drugs in short supply are available as low-cost generics. Also, the medications had a median time of being on the market of 35 years. Several factors have contributed to recent shortages. In 2017, when Hurricane Maria caused mass devastation in Puerto Rico, it affected 5 of the world’s top 10 drug manufacturers and 11 of the top 20 products in the world. The Drug Enforcement Administration (DEA) has placed restrictions on injectable opioids, including those used for anesthesia (ex. fentanyl, hydromorphone, and morphine), due to the opioid crisis. When manufacturers cease production of a generic drug, even temporarily, other manufacturers usually aren’t able to generate additional volumes to make up for the deficit. Some medications are more prone to be in short supply. Typically, these are drugs that don’t make a high profit, don’t have a large market or have long-expired patents. Sterile injectable drugs, such as morphine, anesthetics, antibiotics, electrolytes, sterile saline and cancer drugs, must be produced in sophisticated, sterile facilities. There aren’t enough of these facilities to meet the demand for these medications, which means injectables represent 72% of the drug shortages. One big issue is that are logistical and regulatory challenges that make it difficult for the market to recover from production disruption. In addition, the market doesn’t reward drug manufacturers for prioritizing continuous improvements and early detection of supply chain issues. This means that they don’t have any reason to prevent shortages from occurring.
An important finding in the FDA report was that the drugs most likely to experience shortages had lower prices and were financially unattractive for manufacturers. The report goes into further detail that in the year before a drug experienced a shortage, the median per unit price of all of the 163 drugs reviewed was $8.73. Injectable drugs had a median per unit price of $11.05 and pills were $2.27. Even with the scarcity of drugs in a shortage or at risk for shortage, there isn’t an increase in price that is typically predicted by basic economic principles. This means that just because there is a shortage, the prices don’t rise substantially, so there’s little incentive for manufacturers to increase production or stay in production. This is very true for manufacturers of older generic drugs, in particular. They face intense price competition, uncertain revenue streams and high investment requirements. All of this limit potential returns. This is why older drugs are discontinued in favor of newer, more profitable drugs. Issues arise when one company discontinues a medication because it’s difficult for remaining manufacturers to increase production quickly enough to replace the deficit. When a company stops making a certain medication, then it leaves only one or two companies left to supply the drugs for the entire country. This creates a fragile supply chain that isn’t strong enough to handle market demand. Despite the issues related to price, the FDA primarily points to quality/manufacturing issues as the reason behind shortages, since that was a reason in over 62% of the shortages. According to the Healthcare Supply Chain Association, they estimate the number is even higher at 70%. The FDA also elude to production delays, often caused by not receiving raw materials and components from suppliers. Part of both of these issues is our growing dependence on drugs being manufactured abroad. Over 66% of the key ingredients in American drugs are now manufactured overseas. Per the FDA study, 88% of the manufacturing sites making active pharmaceutical ingredients and 63% of sites making finished dosage forms were located overseas in 2018. This presents not only quality control problems, but a national security risk. Recently, there was a massive recall of blood pressure medications tainted with a probable carcinogen. The source of the contamination was traced to plants in China and India. This is the result of not having high enough standards for offshore companies who produce medication. The reason this has been allowed to happen is because price is the number one focus of buyers and the drug companies want to maintain their profit margins. While this is definitely not acceptable, there isn’t desire or enough infrastructure to improve quality and safety.
There are several ways that manufacturers try to trim expenses. They often merger with other companies and hesitate to invest in the latest production equipment. For example, in 2015, Pfizer bought Hospira, which makes them the largest maker of sterile injectable drugs on the planet. Out of all of their locations, just one plant, in McPherson, Kansas, makes 75% of America’s supply of injectable opioids. The problem is that this facility is over 40 years old and has been struggling with quality problems. In early 2017, the plant was closed for 3 months so upgrades and repairs could be made. Later in 2017, Pfizer was impacted by Hurricane Maria. Their facility in Puerto Rico has some production overlap with McPherson, so when you combine the damage there with quality problems at McPherson, it made existing shortages worse. A year later, Pfizer was still trying to sort everything out.
The main ones impacted by these drug shortages that most people tend to forget about are the patients. People can’t get their regular medication, which makes drug shortages a daily struggle that could easily become life-threatening. According to a study published in The Journal of the American Medical Association (JAMA), the norepinephrine shortage that occurred in 2011 and 2012 increased deaths by 3.7 percentage points and the estimated loss of $13.7 billion nationwide. The FDA report cites a survey that found 56% of American community hospitals said they had delayed or changed patient care because of the drug shortages during 2015-2017. Another survey of nearly 300 pharmacy directors, managers and purchasers showed that 75% of them reported delaying a patient’s treatment because of a drug shortage, 71% reported they were unable to provide patients with a recommended drug and 47% said they feel drug shortages resulted in patients receiving less effective treatments. When a patient is unable to get a required drug or get it in sufficient quantity, they have to find an alternative or take a subtherapeutic dose, which means that they’re not receiving the most appropriate and best care. Another factor is that pharmacists and providers are spending significant amounts of time researching alternatives to the desired drug therapies. The likelihood of errors occurring because of changes in concentration, the need for compounding unavailable doses or the use of multiple dose vials increases significantly during a medication shortage. A survey by the Institute for Safe Medication Practices showed that 21% of all pharmacist and pharmacy worker knew of at least 1 medication error related to a drug shortage. The financial burden also impacts pharmacies and hospitals because for them to maintain an adequate supply of inventory, they must purchase greater quantities than needed. This increases both the chance of outdated inventory and the cost of drugs. The time clinical teams have to spend managing shortages are significant and can also create a financial strain. This can be exceptionally difficult because of the lack of advanced warnings about impending shortages and needing to find less desirable or unfamiliar drugs that are often more expensive. Typically, when products that are in short supply that return to the market, they’re costlier than before the shortage, which only adds to the financial burdens.
Even though there are many factors that are influencing these medications shortages, there has to be something that we can do, right? The FDA is trying to, but further improvements are needed. Until recently, they had a drug approval backlog that took most new manufacturers of existing drugs more than four years to move through, which means the options for the public were limited while compromising the national supply of these medications and led to spectacular price increases. In response to the shortages, the agency has fast-tracked approvals in those categories. This has led to a nearly 17% increase of drugs on the market and cut average time of reviews for new drug applications by 6 months. In addition, the FDA started publishing a list of drugs that are off patent and lacking generic competition, which provides manufacturers with opportunities to start making new products. In response to 2011 being the highest year on record with drug shortages, Congress passed the FDA Safety and Innovation Act in 2012. One of the important things that this Act requires is that drug manufactures must notify the FDA of any permanent or temporary interruption in production. The agency can use these notifications to work with other manufacturers to see if any of them have extra capacity to make the medication that might be short. However, the agency doesn’t have the power to add capacity or new suppliers, which means they can’t force a company to keep making a drug it wants to discontinue. Another option is to extend the expiration date of a medication that is short. In order to do this, a manufacturer has to have data to saying that the medication is safe for consumers and the FDA needs to review this information before approving the extension. The thought is that this will help to increase supplies until new production is available. Another proposed solution was to introduce quality ratings for drug companies. This would help companies with good quality ratings attract higher prices and increase their market share. Part of this solution includes contract agreements in which the companies receive a minimum return on their investment for having facilities with high quality ratings. Critics of this solution say that this wouldn’t really help because it’s voluntary and not mandatory. A different option is to shift some of the financial risk and uncertainty away from manufactures, especially for older generics, and back onto purchasing organizations. There are a couple of ways to do this, such as by requiring purchasers to buy a minimum volume of the drugs and encouraging hospitals to pay higher prices for older generics. Other things to consider include harmonizing guidelines for pharmaceutical quality systems, improving data sharing/risk management and lengthening expiration dates (for drugs that have been proven to be safe beyond their current expiration dates—this would decrease the need for the FDA to approve this process for as many medications as possible). A different idea that has the attention of both the FDA and drug manufactures is continuous manufacturing (CM). The current method is batch processing, which takes the various components of a drug and brings them together through a step-by-step process. The issue is that the current batch must finish before a subsequent batch can be processed. Often there are several steps in the process that are completed with several different pieces of equipment. So, this is time consuming and introduces the potential for errors in each one of the steps. Continuous manufacturing takes the base ingredients to the final product with no need to stop during production. So, there’s no need to shut down equipment and no down time as the product is created. Not only is this more efficient and safer, it’s less expensive. While all of these recommendations are good, if you take a closer look, you realize that they don’t involve any direct government action, but rely on the drug companies and others in the healthcare industry to make changes. This is why many individuals in the pharmaceutical arena feel that the recommendations aren’t strong enough to produce a significant impact.
To help prevent future drug shortages, the researchers had recommendations for the healthcare industry as well. It’s important for healthcare providers to employ a formal, standard process to address the issue of drug shortages. The first step is to assess the inventory of drugs on hand and estimate how long the supply will last based on historical usage. This will help to identify drug shortages early by being alert to signs of a potential impending shortage, like partially filled orders or specific strengths of drugs that are difficult to obtain. Part of this step is to engage in ongoing communication with staff members and determine key individuals responsible for staying up-to-date on drug shortages. One other suggestion was to establish a drug shortage network with local healthcare providers to share information regarding drug shortages and alternative products. Also, don’t overstock drugs because stockpiling may actually lead to an artificial shortage. The next step is to find potential therapeutic alternatives early while prioritizing patients who need the unavailable medication and place limitations on using it. When using alternative therapies, it’s critical to assess the potential hazards to patients and the organization and then determine how to best manage the risk of these adverse effects and potential serious errors. The last, but a very vital step, is to talk to patients about drug shortages. Not only should you inform them of the shortage, but discuss the causes and expected duration. Some hospitals and health plans are coming up with their own solutions. Civica Rx is a nonprofit consortium of hospitals and health plans. By combining their need for common generics, they hope to create their own market where they can contract with producers to guarantee minimum purchases at a rate that’s beneficial to all involved.
There’s no question that chronic drug shortages threaten patient care. These shortages are caused by significantly low prices for older generic medicines and a health care marketplace that doesn’t run on the rules of supply and demand. Some industry officials also say that inadequate planning during drug company mergers and manufacturers limiting supplies to increase demand and bolster profits also play a role. One of the hardest things is identifying what medications will be impacted, how that will affect care delivery/patient safety and when will a shortage occur. The FDA task force stated that shortages are likely to continue unless there are dramatic changes to the broken marketplace. As a society, we need to start viewing essential medications as critical infrastructure. They’re not any different from electricity and water. Changes to the system need to be made and they need to be made now or more lives could be lost.